The rhinoviruses were first isolated 50 years ago from individuals with common cold symptoms. Subsequent studies have defined the epidemiology and clinical implications of these infections. Rhinovirus infections occur year round with seasonal peaks of incidence in the early fall, usually September to November, and again in the spring from March to May. During these periods of increased incidence, up to 80% of common cold illnesses may be associated with a documented rhinovirus infection [1]. The characteristic clinical syndrome associated with rhinovirus infection is the common cold, and the rhinoviruses are responsible for at least 50% of these illnesses. Although common colds are of little direct medical consequence, they are associated with enormous cost to society in the form of missed school and work and unnecessary medical care. The medical implications of rhinovirus infection are not, however, limited to the common cold. One-third of children with acute otitis media have evidence of concurrent rhinovirus infection, including 25% who have evidence of virus in the middle ear fluid [2]. Some of these children also have bacteria isolated from the middle ear, suggesting that rhinovirus infection may cause otitis media directly or by predisposing to bacterial infection. Sinusitis is less well studied, but it seems likely that rhinovirus may play a similar role in this syndrome. A study of young adults with uncomplicated common colds found that most had involvement of the sinuses detectable by computed-tomography scanning and that these abnormalities resolved in all cases without antibacterial treatment [3].

In addition to these upper respiratory tract syndromes, rhinovirus infection has also been associated with lower respiratory tract symptoms. It is widely accepted that rhinovirus is an important cause of asthma exacerbations in school-aged children. Rhinovirus infection is associated with 60%–70% of the asthma exacerbations in this age group [4, 5]. Rhinovirus also appears to play a role in exacerbations of cystic fibrosis in children and of chronic bronchitis in adults. The potential role of rhinovirus infections as a cause of pneumonia in immunocompetent children or immunocompromised patients is more controversial. Rhinovirus grows best in cell culture at ∼33C°. This preferential growth at lower temperature has long been cited to suggest that rhinovirus might not infect the lower airways. This concept was supported by early studies demonstrating that infection was more readily produced when virus was administered by intranasal drops than by aerosol. More-recent studies have established that, under experimental conditions, rhinovirus can replicate in the lower respiratory tract, but the frequency of lower tract involvement during natural infection remains unknown. A potential role for rhinovirus as a cause of lower respiratory tract infections is also supported by detection of rhinovirus by either culture or polymerase chain reaction (PCR) in several studies of children with lower respiratory tract disease [6]–[8]. Most of these studies have found rhinovirus in <10% of patients, and in many cases other pathogens more commonly associated with lower respiratory tract symptoms were also isolated. Whether the rhinovirus is a primary cause of the lower respiratory tract disease in these children or whether rhinovirus infection of the upper respiratory tract predisposes to bacterial infection of the lower respiratory tract remains unsettled.

The study by Miller et al. [9, in this issue of the Journal, defines the epidemiological and clinical findings in hospitalized infants and children who were infected with rhinovirus. The reported frequency of infection, seasonal pattern of incidence, and association of infection with wheezing and asthma exacerbation are consistent with previous reports. In contrast, the frequent association of rhinovirus with fever, pneumonia, gastrointestinal symptoms, or sepsis in this study is a distinct departure from the previous concept of rhinovirus as a common cold virus. The conclusion that these clinical syndromes were caused by rhinovirus should be approached with caution.

Recent prospective cohort studies using sensitive diagnostic techniques for detection of infection have expanded our understanding of rhinovirus infection in infants and children. Two studies evaluated the incidence of infection during respiratory illnesses and at intermittent visits for routine care in the first 2 years of life [10, 11]. These studies reported the incidence of infection in this age group to be 0.7–0.8 infections/year. A similar but more recent report in infants <1 year of age found an incidence of 2 infections/year [12]. Ten to twenty-three percent of the infections in these studies were detected in infants judged to be asymptomatic. A longitudinal surveillance study in a small cohort of young children found an average incidence of picornavirus infection of 6/ year, with 20% of the infections judged to be asymptomatic [13]. Rhinovirus was detected by PCR for 1–3 weeks around each infection. In light of the prevalence of rhinovirus infection in the pediatric population, incidental detection of virus during an unassociated hospitalization may occur with some frequency. As noted by Miller et al., examination of a control population of children hospitalized for noninfectious illness would assess this possibility.

Another consideration in evaluating the results of this study is the possibility that rhinovirus infection may predispose to infection with bacterial pathogens. There is substantial clinical and epidemiological evidence to suggest that viral infections may predispose to bacterial superinfection. Although data describing an association between rhinovirus and bacterial infection are limited, rhinovirus infection does increase the adherence of Streptococcus pneumoniae to airway epithelial cells [14]. That bacterial diagnoses were not established in the study by Miller et al. must be viewed in light of the insensitivity of the diagnostic methods for detection of bacterial pneumonia. This problem was recently highlighted by a report suggesting that immunization against pneumococcus prevents almost one-third of “viral” pneumonias [15].

The rhinoviruses are among the most common causes of infection of humankind, but these infections have traditionally been viewed as having little medical consequence. The increased diagnostic sensitivity provided by PCR is changing this perception. It is clear that rhinovirus is an important cause of otitis media and sinusitis and can precipitate exacerbations of asthma in children. The report of Miller et. al. suggests that rhinovirus infection may play role in other illnesses that result in hospitalization of young children. This report should stimulate additional studies to define the contribution of rhinovirus infection to these illnesses.

References

1.
Arruda
E
Pitkaranta
A
Witek
TJ
Jr
Doyle
CA
Hayden
FG
Frequency and natural history of rhinovirus infections in adults during autumn
J Clin Microbiol
 , 
1997
, vol. 
35
 (pg. 
2864
-
8
)
2.
Pitkaranta
A
Arruda
E
Malmberg
H
Hayden
FG
Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR
J Clin Microbiol
 , 
1997
, vol. 
35
 (pg. 
1791
-
3
)
3.
Gwaltney
JM
Jr
Phillips
CD
Miller
RD
Riker
DK
Computed tomographic study of the common cold
N Engl J Med
 , 
1994
, vol. 
330
 (pg. 
25
-
30
)
4.
Johnston
SL
Pattemore
PK
Sanderson
G
, et al.  . 
Community study of role of viral infections in exacerbations of asthma in 9–11 year old children [comments]
BMJ
 , 
1995
, vol. 
310
 (pg. 
1225
-
9
)
5.
Rakes
GP
Arruda
E
Ingram
JM
, et al.  . 
Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care: IgE and eosinophil analyses
Am J Respir Crit Care Med
 , 
1999
, vol. 
159
 (pg. 
785
-
90
)
6.
El-Sahly
HM
Atmar
RL
Glezen
WP
Greenberg
SB
Spectrum of clinical illness in hospitalized patients with “common cold” virus infections
Clin Infect Dis
 , 
2000
, vol. 
31
 (pg. 
96
-
100
)
7.
Juven
T
Mertsola
J
Waris
M
, et al.  . 
Etiology of community-acquired pneumonia in 254 hospitalized children
Pediatr Infect DisJ
 , 
2000
, vol. 
19
 (pg. 
293
-
8
)
8.
Michelow
IC
Olsen
K
Lozano
J
, et al.  . 
Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children
Pediatrics
 , 
2004
, vol. 
113
 (pg. 
701
-
7
)
9.
Miller
EK
Lu
X
Erdman
DD
, et al.  . 
Rhinovirus-associated hospitalizations in young children
J Infect Dis
 , 
2007
, vol. 
195
 (pg. 
773
-
81
(in this issue)
10.
Blomqvist
S
Roivainen
M
Puhakka
T
Kleemola
M
Hovi
T
Virological and serological analysis of rhinovirus infections during the first two years of life in a cohort of children
J Med Virol
 , 
2002
, vol. 
66
 (pg. 
263
-
8
)
11.
van Benten
I
Koopman
L
Niesters
B
, et al.  . 
Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants
Pediatr Allergy Immunol
 , 
2003
, vol. 
14
 (pg. 
363
-
70
)
12.
Kusel
MM
de Klerk
NH
Holt
PG
Kebadze
T
Johnston
SL
Sly
PD
Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study
Pediatr Infect Dis J
 , 
2006
, vol. 
25
 (pg. 
680
-
6
)
13.
Winther
B
Hayden
FG
Hendley
JO
Picornavirus infections in children diagnosed by RT-PCR during longitudinal surveillance with weekly sampling: association with symptomatic illness and effect of season
J Med Virol
 , 
2006
, vol. 
78
 (pg. 
644
-
50
)
14.
Ishizuka
S
Yamaya
M
Suzuki
T
, et al.  . 
Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells
J Infect Dis
 , 
2003
, vol. 
188
 (pg. 
1928
-
39
)
15.
Madhi
SA
Klugman
KP
A role for Streptococcus pneumoniae in virus-associated pneumonia
Nat Med
 , 
2004
, vol. 
10
 (pg. 
811
-
3
)
Potential conflicts of interest: R.B.T. reports no conflicts of interest with regard to the subject of this editorial. He has received research funding from the Dial Corporation and Warner Lambert Company and is a consultant to Procter & Gamble Company and Schering Plough Research Institute.